Assessment of Radiation Doses Delivered to Organs at Risk Among Patients With Early-Stage Favorable Hodgkin Lymphoma Treated With Contemporary Radiation Therapy

Abstract

IMPORTANCE Response-adapted randomized trials have used positron emission tomographycomputed tomography to attempt to identify patients with early-stage favorable Hodgkin lymphoma (ESFHL) who could be treated with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) without radiation therapy (RT). While maximal efficacy is demonstrated with combined modality therapy, RT is often omitted in fear of late adverse effects; however, the application of modern RT could limit these toxic effects. OBJECTIVE To determine the radiation doses delivered to organs at risk with modern involved-site RT among patients with ESFHL treated with 20 Gy after 2 cycles of ABVD. DESIGN, SETTING, AND PARTICIPANTS This case series included 42 adult patients with ESFHL (according to the German Hodgkin Study Group criteria) who were treated between 2010 and 2019, achieved complete response by positron emission tomography-computed tomography (1-3 on 5-point scale) following 2 cycles of ABVD, and then received consolidative RT. The study was conducted at a single comprehensive cancer center. EXPOSURES 2 cycles of chemotherapy followed by 20-Gy involved-site RT. MAIN OUTCOMES AND MEASURES The medical records of patients with ESFHL were examined. Organs at risk were contoured, and doses were calculated. Progression-free survival, defined from date of diagnosis to disease progression, relapse, or death, and overall survival were estimated using the Kaplan-Meier method. RESULTS The cohort comprised 42 patients with ESFHL (median [range] age at diagnosis, 35 [18-74] years; 18 [43%] women; 24 [57%] with stage II disease). At a median follow-up of 44.6 (95% CI, 27.6-61.6) months, the 3-year progression-free survival and overall survival rates were 91.2% (95% CI, 74.9%-97.1%) and 97.0% (95% CI, 80.4%-99.6%), respectively. The mean heart dose was less than 5 Gy (mean, 0.8 Gy; SD, 1.5 Gy; range, 0-4.8 Gy) in all patients. The mean (SD) breast dose for both breasts was 0.1 (0.2) Gy (left breast range, 0-1.0 Gy; right breast range, 0-0.9 Gy). CONCLUSIONS AND RELEVANCE In this study, combined modality therapy with 2 cycles of ABVD and 20 Gy for ESFHL was highly effective and avoided excess doses to organs at risk, which may limit long-term toxic effects.

Predicted Risks of Cardiovascular Disease Following Chemotherapy and Radiotherapy in the UK NCRI RAPID Trial of Positron Emission Tomography–Directed Therapy for Early-Stage Hodgkin Lymphoma

“…However, the magnitude of the risk varies widely and, for a majority of patients, the benefit of reduced HL relapse substantially outweighs the risk of CVD. With more modern radiotherapy techniques, the cardiovascular radiation doses achieved 35 would result in even lower predicted risks than those seen for the RAPID cohort. As the sites of disease and degree of mediastinal involvement are known at diagnosis, the radiation doses to cardiovascular organs, and hence the risk of radiation-related CVD, can be estimated when the initial treatment strategy is decided.…”

“…It should be noted that developments in radiotherapy techniques since the RAPID trial, including smaller target volumes, 32 the use of deep-inspiration breath-hold techniques, 33 optimized intensity-modulated radiotherapy, 34 and proton beam therapy, 18 have reduced irradiated volumes and radiation doses to normal tissues, especially when combined with a 20 Gy prescribed dose for favorable ES-HL. 35 Radiation-related CVD is not the only late side effect that may be reduced by the omission of radiotherapy. Risks of second cancers and other radiation-related late toxicities such as xerostomia and hypothyroidism, which would also be reduced by a chemotherapy-only approach, are also likely to be lower with contemporary radiotherapy, but a comprehensive assessment of late toxicities goes beyond the scope of this study.…”

Informing radiotherapy decisions in stage I/IIa Hodgkin lymphoma: modeling life expectancy using radiation dosimetry

“… 18,22 The result is that, for contemporary cohorts, the radiation doses to OARs are substantially lower than those examined here. 23 …”

“…18,22 The result is that, for contemporary cohorts, the radiation doses to OARs are substantially lower than those examined here. 23 There are, of course, many caveats to our modeling approach and the assumptions made. The use of population-derived incidence and case-fatality rates assumes equivalence between radiationinduced disease and general population disease.…”

Mechanisms and Insights for the Development of Heart Failure Associated with Cancer Therapy

“…Advancements such as these have resulted in a marked reduction in cardiac exposure. For example, in HL, the MHD was typically ≥35 Gy with historic techniques [ 41 ]; in contrast, it is typically in the single digits with a modern RT approach [ 80 ].…”